ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2010) 24 OC2.1

Space-time clustering of elevated TSH levels on newborn screening

M Pearce1, R McNally1, J Day2, M Korada3, S Turner4 & T Cheetham5


1Institute of Health and Society, University of Newcastle upon Tyne, Newcastle upon Tyne, UK; 2Department of Clinical Biochemistry, University Hospital of North Durham, Durham, Durham, UK; 3Department of Paediatric Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK; 4Department of Clinical Biochemistry, Royal Victoria Infirmary, Newcastle Upon Tyne, UK; 5Institute of Human Genetics, Newcastle University, Institute of Human Genetics, Newcastle University, Centre for Life, Central Parkway, Newcastle-upon-Tyne, UK.


Introduction: Studies have reported a rising incidence of congenital hypothyroidism (CHT) although the pathophysiology of most cases is unknown. A rising incidence is not simply a reflection of changing assay methodology and environmental factors may have an aetiological role. If so, then cases may exhibit space-time clustering, where cases occur at similar times and close proximities to other cases.

Methods: We investigated whether there is evidence of space-time clustering of elevated thyroid stimulating hormone (TSH) in newborns. Around 35,000 infants are screened every year in this single centre by measuring blood spot TSH levels. The study region represents a mixture of heavily populated areas and widespread rural communities and has a population of 3.1 million. Data on cases, including dates of birth and postal (zip) code, were available from 1st January 1994 and 31st March 2006. The data were analysed using space-time clustering statistical methods (geographical distance and nearest neighbour/NN approaches).

Results: Data on 207 cases of elevated TSH values, a proxy for CHT and the most robust single marker of abnormal gland development or function, were available from 1994 to 2006 inclusive. We established that more than 93% of infants had raised serum TSH values (>5 mU/l). Analysis showed statistically significant evidence of space-time clustering (P=0.005 and P=0.02, using geographical distance and NN threshold approaches respectively). Clustering was most marked for cases born within 0.1 – 0.5 year (1–6 months) of one another.

Conclusions: This is the first study to find significant space-time clustering of cases of elevated TSH levels in newborns, a surrogate for space-time clustering of CHT. Whilst the reasons for the clustering are unclear, it would appear from this analysis that environmental exposures are likely to be involved, although environmental determinants of genetic mutations and epigenetic factors cannot be ruled out.

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